Zollinger-Ellison Syndrome (ZES) is severe peptic ulcer disease secondary to gastric acid hypersecretion due to unregulated gastrin release from a gastrinoma. Elevated gastrin leads to overstimulation of histamine-secreting enterochromaffin-like cells and subsequent stimulation of parietal cell production of hydrochloric acid. Long-standing hypersecretion of gastric acid leads to peptic ulcer disease, erosive esophagitis, and diarrhea.

The incidence of ZES ranges from 0.1%-1% of patients with peptic ulcer disease and is more common in males than in females. Most patients are diagnosed between ages 20-50, although the time span from symptoms to diagnosis is typically greater than 5 years due to the wide availability of acid-suppressing medications. 70%-80% of gastrinomas are sporadic, and 20%-30% are secondary to multiple endocrine neoplasia type 1 (MEN1). Gastrinomas typically arise in the duodenum and are one of the most common functional pancreatic neuroendocrine tumors. In contrast with pancreatic gastrinomas, duodenal gastrinomas are generally small (<1 cm), often multiple, and more likely to have metastasized to the liver at the time of diagnosis. In a small percentage of patients, gastrinomas arise in a nonpancreatic or nonduodenal site, including the stomach and ovary.

Abdominal pain and chronic diarrhea are the most common presenting symptoms of ZES, each seen in approximately 75% of patients. Other common symptoms include heartburn, weight loss, and gastrointestinal bleeding.